Selection of mouse strains showing high and low-incidences of alloxan-induced diabetes and quantitative morphological analysis of Langerhan's islands in two strains

To produce a disease model for humans, especially an experimental model of diabetes in animals, ICR mice were inbred until the 20th generation by two-ways selection to produce high- and low-incidences of alloxan-induced diabetes. Alloxan-induced diabetes is known to be a representative form of experimental diabetes. The results obtained were summarized as follows. 1. The incidence of alloxan-induced diabetes in F20 was 98.9 % in the high-incidence strain and 0 % in the low-incidence strain. Changes in successive generations in the incidence of diabetes were studied. In the high-incidence strain, it was 98.7 % in F13 and in the low-incidence strain, it reached 0 % in F7, remaining near that level in later generations. The values of ED50 used in this study seemed to reach the selection limit in mating, showing a 98.6 % inbreeding coefficient at the 20th generation. 2. The blood glucose level in F20 was 455 ml/dl in the high-incidence strain and 127 mg/dl in the low-incidence strain. Changes in successive generations in blood glucose levels were studied. In the high-incidence strain, it was 395 mg/dl in F8, ranging thereafter between 350 and 400 mg/dl, and in the low-incidence strain, it was 128 mg/dl in F12, then varing from 120 to 140 mg/dl in following generations. 3. In the high and low-incidence strains, quantitative morphological analysis was done in the area of Langerhan's island (islets) in the pancreatic area (100 cm2), no. of islets and no. of beta cells in an islet. In a non-treated control, any measurements were significantly higher in the low-incidence strain than in the high-incidence strain. Similar trends were observed in the alloxan-treated experiment. These results indicate that the high and low-incidence strains with successive two-way selection toward sensitivity to alloxan have constituted a characteristic feature of quantitative morphological peculiarity in pancreatic tissue